9-134825776-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000093.5(COL5A1):c.4955-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,567,832 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 58 hom., cov: 34)

Exomes 𝑓: 0.0019 ( 63 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.456

Variant links:

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

COL5A1 links:

LOC101448202 (HGNC:):

LOC101448202 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 9-134825776-C-T is Benign according to our data. Variant chr9-134825776-C-T is described in ClinVar as [Benign]. Clinvar id is 136905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134825776-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.4955-16C>T	intron_variant	Intron 62 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.4955-16C>T	intron_variant	Intron 62 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.4955-16C>T	intron_variant	Intron 62 of 64		XP_016869755.1
LOC101448202	NR_103451.2 link	n.71-5567G>A	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL5A1	ENST00000371817.8 link	c.4955-16C>T	intron_variant	Intron 62 of 65	1	NM_000093.5	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4 link	c.4955-16C>T	intron_variant	Intron 62 of 65	2		ENSP00000360885.4	P20908-2H7BY82
COL5A1	ENST00000460264.5 link	n.423-16C>T	intron_variant	Intron 3 of 4	3
COL5A1	ENST00000465877.1 link	n.135-16C>T	intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2412

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0545

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00454

AC:

1138

AN:

250890

Hom.:

AF XY:

0.00324

AC XY:

440

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.0552

Gnomad AMR exome

AF:

0.00481

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000441

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00187

AC:

2649

AN:

1415498

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1137

AN XY:

706808

show subpopulations

Gnomad4 AFR exome

AF:

0.0542

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000259

Gnomad4 FIN exome

AF:

0.000208

Gnomad4 NFE exome

AF:

0.000322

Gnomad4 OTH exome

AF:

0.00419

GnomAD4 genome

AF:

0.0159

AC:

2420

AN:

152334

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1106

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0545

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00912

Hom.:

Bravo

AF:

0.0176

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jul 21, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 15, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Aug 11, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:2

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibromuscular dysplasia, multifocal

Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.3

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over